Calcium release channel RyR2 regulates insulin release and glucose homeostasis

Journal of Clinical Investigation

Volumn 125, Issue 5, 2015, Pages 1968-1978

  Santulli, Gaetano ^a   Pagano, Gennaro ^b,c,d   Sardu, Celestino ^e,f,g   Xie, Wenjun ^a   Reiken, Steven ^a   D'Ascia, Salvatore Luca ^h   Cannone, Michele ⁱ   Marziliano, Nicola ^j,k   Trimarco, Bruno ^d   Guise, Theresa A ^l   Lacampagne, Alain ^m   Marks, Andrew R ⁿ  

^a Columbia University Medical Center ^*  (United States)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF MOLISE   (Italy)

^d UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^e LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^f SECOND UNIVERSITY OF NAPLES   (Italy)

^g CATHOLIC UNIVERSITY   (Italy)

^h Department of Cardiology and Arrhythmology   (Italy)

ⁱ Department of Anesthesia and Intensive Care   (Italy)

^j OSPEDALE NIGUARDA CA GRANDA   (Italy)

^k UNIVERSITY HOSPITAL OF PARMA   (Italy)

^l INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^m INSERM   (France)

ⁿ Och Spine at New York Presbyterian Hospitals   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR6.2; RYANODINE RECEPTOR 2; UNCOUPLING PROTEIN 2; X BOX BINDING PROTEIN 1; CALCIUM; GLUCAGON; GLUCOSE; INSULIN; RYANODINE RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA; CLINICAL ARTICLE; CONTROLLED STUDY; DIET RESTRICTION; ENDOPLASMIC RETICULUM STRESS; GENE MUTATION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE INTOLERANCE; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; HUMAN; INSULIN RELEASE; MALE; MITOCHONDRIAL RESPIRATION; MOUSE; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; UPREGULATION; ADULT; AMINO ACID SUBSTITUTION; ANIMAL; FEMALE; GENETICS; HEART VENTRICLE TACHYCARDIA; HOMEOSTASIS; ION TRANSPORT; METABOLISM; MISSENSE MUTATION; MITOCHONDRION; MOUSE MUTANT; NITROSATION; NON INSULIN DEPENDENT DIABETES MELLITUS; OXIDATION REDUCTION REACTION; PHYSIOLOGY; POINT MUTATION; SECRETION (PROCESS); TRANSGENIC MOUSE; YOUNG ADULT;

ADULT; AMINO ACID SUBSTITUTION; ANIMALS; CALCIUM; DIABETES MELLITUS, TYPE 2; ENDOPLASMIC RETICULUM STRESS; FEMALE; GLUCAGON; GLUCOSE; GLUCOSE INTOLERANCE; HOMEOSTASIS; HUMANS; INSULIN; ION TRANSPORT; ISLETS OF LANGERHANS; MALE; MICE, OBESE; MICE, TRANSGENIC; MITOCHONDRIA; MUTATION, MISSENSE; NITROSATION; OXIDATION-REDUCTION; POINT MUTATION; RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL; TACHYCARDIA, VENTRICULAR; YOUNG ADULT;

EID: 84928994366     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI79273     Document Type: Article

References (76)

1. Santulli G, et al. Age-related impairment in insulin release: the essential role of β(2)-adrenergic receptor. Diabetes. 2012;61(3):692-701.
2. Prentki M, Nolan CJ. Islet β cell failure in type 2 diabetes. J Clin Invest. 2006;116(7):1802-1812.
3. Rutter GA, Pinton P. Mitochondria-associated endoplasmic reticulum membranes in insulin signaling. Diabetes. 2014;63(10):3163-3165.
4. Wollheim CB, Maechler P. β-Cell mitochondria and insulin secretion: messenger role of nucleotides and metabolites. Diabetes. 2002;51(suppl 1):S37-S42.
5. Ashcroft FM, Rorsman P. K(ATP) channels and islet hormone secretion: new insights and controversies. Nat Rev Endocrinol. 2013;9(11):660-669.
6. De Marchi U, Thevenet J, Hermant A, Dioum E, Wiederkehr A. Calcium co-regulates oxidative metabolism and ATP synthase-dependent respiration in pancreatic β cells. J Biol Chem. 2014;289(13):9182-9194.
7. 2+/calmodulin-dependent protein kinase II reduces glucose-stimulated calcium influx and insulin secretion, impairing glucose tolerance. J Biol Chem. 2014;289(18):12435-12445.
8. Nolan CJ, Madiraju MS, Delghingaro-Augusto V, Peyot ML, Prentki M. Fatty acid signaling in the β-cell and insulin secretion. Diabetes. 2006;55(suppl 2):S16-S23.
9. Henquin JC, Nenquin M, Stiernet P, Ahren B. In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse: pattern and role of cytoplasmic Ca2+ and amplification signals in β-cells. Diabetes. 2006;55(2):441-451.
10. Namkung Y, et al. Requirement for the L-type Ca(2+) channel alpha(1D) subunit in postnatal pancreatic β cell generation. J Clin Invest. 2001;108(7):1015-1022.
11. Gilon P, Chae HY, Rutter GA, Ravier MA. Calcium signaling in pancreatic β-cells in health in Type 2 diabetes. Cell Calcium. 2014;56(5):340-361.
12. 2+ entry. FEBS Lett. 2012;586(1):89-95.
13. Zhang Q, et al. R-type Ca(2+)-channel-evoked CICR regulates glucose-induced somatostatin secretion. Nat Cell Biol. 2007;9(4):453-460.
14. Islam MS. Calcium signaling in the islets. Adv Exp Med Biol. 2010;654:235-259.
15. Bruton JD, et al. Ryanodine receptors of pancreatic β-cells mediate a distinct context-dependent signal for insulin secretion. FASEB J. 2003;17(2):301-303.
16. Johnson JD, Kuang S, Misler S, Polonsky KS. Ryanodine receptors in human pancreatic β cells: localization and effects on insulin secretion. FASEB J. 2004;18(7):878-880.
17. Santulli G, Marks AR. Essential roles of intracellular calcium release channels in muscle, brain, metabolism, aging. Curr Mol Pharmacol. In press.
18. Zalk R, et al. Structure of a mammalian ryanodine receptor. Nature. 2015;517(7532):44-49.
19. Brillantes AB, et al. Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein. Cell. 1994;77(4):513-523.
20. Marks AR. Calcium cycling proteins and heart failure: mechanisms and therapeutics. J Clin Invest. 2013;123(1):46-52.
21. Umanskaya A, Santulli G, Xie W, Andersson DC, Reiken SR, Marks AR. Genetically enhancing mitochondrial antioxidant activity improves muscle function in aging. Proc Natl Acad Sci U S A. 2014;111(42):15250-15255.
22. Fauconnier J, et al. Leaky RyR2 trigger ventricular arrhythmias in Duchenne muscular dystrophy. Proc Natl Acad Sci U S A. 2010;107(4):1559-1564.
23. Lehnart SE, et al. Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak. Circulation. 2004;109(25):3208-3214.
24. Leenhardt A, Denjoy I, Guicheney P. Catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol. 2012;5(5):1044-1052.
25. Santulli G. Classification of syncope-producing cardiac arrhythmias. In: Silva E, Cruz, G, eds. Comas and Syncope: Causes, Prevention and Treatment. New York, New York, USA: Nova Science Publisher; 2012:167-177.
26. Yuan Q, et al. Functional role of Calstabin2 in age-related cardiac alterations. Sci Rep. 2014;(4):7425.
27. Xie W, Santulli G, Guo X, Gao M, Chen BX, Marks AR. Imaging atrial arrhythmic intracellular calcium in intact heart. J Mol Cell Cardiol. 2013;64:120-123.
28. Bellinger AM, et al. Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity. Proc Natl Acad Sci U S A. 2008;105(6):2198-2202.
29. Noguchi N, et al. FKBP12.6 disruption impairs glucose-induced insulin secretion. Biochem Biophys Res Commun. 2008;371(4):735-740.
30. 2+, leading to induction of endoplasmic reticulum stress in pancreatic β-cells. Diabetes. 2005;54(2):452-461.
31. O'Neill CM, et al. Circulating levels of IL-1B+IL-6 cause ER stress and dysfunction in islets from prediabetic male mice. Endocrinology. 2013;154(9):3077-3088.
32. Vetterli L, et al. Delineation of glutamate pathways and secretory responses in pancreatic islets with β- cell-specific abrogation of the glutamate dehydrogenase. Mol Biol Cell. 2012;23(19):3851-3862.
33. Zhang CY, et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, β cell dysfunction, and type 2 diabetes. Cell. 2001;105(6):745-755.
34. Yoshihara E, et al. Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity. Nat Commun. 2010;1:127.
35. Krauss S, et al. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic β cell dysfunction. J Clin Invest. 2003;112(12):1831-1842.
36. Gier B, et al. Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress. J Clin Invest. 2009;119(11):3246-3256.
37. Ye Y, et al. Designing calcium release channel inhibitors with enhanced electron donor properties: stabilizing the closed state of ryanodine receptor type 1. Mol Pharmacol. 2012;81(1):53-62.
38. Mitchell T, et al. Dysfunctional mitochondrial bioenergetics and oxidative stress in Akita(+/Ins2)-derived β-cells. Am J Physiol Endocrinol Metab. 2013;305(5):E585-E599.
39. Tang C, et al. Glucose-induced β cell dysfunction in vivo in rats: link between oxidative stress and endoplasmic reticulum stress. Diabetologia. 2012;55(5):1366-1379.
40. Lombardi A, Inabnet WB 3rd, Owen R, Farenholtz KE, Tomer Y. Endoplasmic reticulum stress as a novel mechanism in amiodarone-induced destructive thyroiditis. J Clin Endocrinol Metab. 2015;100(1):E1-E10.
41. Hara T, Mahadevan J, Kanekura K, Hara M, Lu S, Urano F. Calcium efflux from the endoplasmic reticulum leads to β-cell death. Endocrinology. 2014;155(3):758-768.
42. Perocchi F, et al. MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature. 2010;467(7313):291-296.
43. MacDonald PE, Joseph JW, Rorsman P. Glucose-sensing mechanisms in pancreatic β-cells. Philos Trans R Soc Lond B Biol Sci. 2005;360(1464):2211-2225.
44. Wiederkehr A, Wollheim CB. Mitochondrial signals drive insulin secretion in the pancreatic β-cell. Mol Cell Endocrinol. 2012;353(1-2):128-137.
45. Jitrapakdee S, Wutthisathapornchai A, Wallace JC, MacDonald MJ. Regulation of insulin secretion: role of mitochondrial signalling. Diabetologia. 2010;53(6):1019-1032.
46. Anello M, et al. Functional and morphological alterations of mitochondria in pancreatic β cells from type 2 diabetic patients. Diabetologia. 2005;48(2):282-289.
47. Dror V, et al. Glucose and endoplasmic reticulum calcium channels regulate HIF-1β via presenilin in pancreatic β-cells. J Biol Chem. 2008;283(15):9909-9916.
48. Johnson JD, Bround MJ, White SA, Luciani DS. Nanospaces between endoplasmic reticulum and mitochondria as control centres of pancreatic β- cell metabolism and survival. Protoplasma. 2012;249(suppl 1):S49-S58.
49. Yoon JC, et al. Suppression of beta cell energy metabolism and insulin release by PGC-1α. Dev Cell. 2003;5(1):73-83.
50. Shimomura K, et al. Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects. Diabetes. 2006;55(6):1705-1712.
51. Bonnefond A, et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet. 2012;44(3):297-301.
52. Hu FB, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med. 2001;345(11):790-797.
53. Langenberg C, et al. Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study. PLoS Med. 2014;11(5):e1001647.
54. Saxena R, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42(2):142-148.
55. Fadista J, et al. Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism. Proc Natl Acad Sci U S A. 2014;111(38):13924-13929.
56. Sladek R, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445(7130):881-885.
57. Vaxillaire M, et al. Type 2 diabetes-related genetic risk scores associated with variations in fasting plasma glucose and development of impaired glucose homeostasis in the prospective DESIR study. Diabetologia. 2014;57(8):1601-1610.
58. DIAbetes Genetics Replication Meta-Analysis (DIAGRAM) Consortium, et al. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet. 2014;46(3):234-244.
59. Palmer ND, et al. A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One. 2012;7(1):e29202.
60. Pontoglio M, et al. Defective insulin secretion in hepatocyte nuclear factor 1α-deficient mice. J Clin Invest. 1998;101(10):2215-2222.
61. Kulkarni RN, et al. Altered function of insulin receptor substrate-1-deficient mouse islets and cultured β-cell lines. J Clin Invest. 1999;104(12):R69-R75.
62. Wu Y, et al. Growth hormone receptor regulates β cell hyperplasia and glucose-stimulated insulin secretion in obese mice. J Clin Invest. 2011;121(6):2422-2426.
63. Robertson RP, et al. Assessment of β-cell mass alpha- beta-cell survival function by arginine stimulation in human autologous islet recipients. Diabetes. 2014;64(2):565-572.
64. Kerouz NJ, Horsch D, Pons S, Kahn CR. Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. J Clin Invest. 1997;100(12):3164-3172.
65. Santulli G. Coronary heart disease risk factors and mortality. JAMA. 2012;307(11):1137.
66. Sardu C, Marfella R, Santulli G. Impact of diabetes mellitus on the clinical response to cardiac resynchronization therapy in elderly people. J Cardiovasc Transl Res. 2014;7(3):362-368.
67. Santulli G. Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus. Neurology. 2012;78(11):840.
68. Badimon L, Hernandez Vera R, Vilahur G. Determinants of cardiovascular risk in diabetes beyond hyperglycemia. J Cardiovasc Dis. 2013;1(2):53-62.
69. Santulli G. Beta-blockers in diabetic patients with heart failure. JAMA Intern Med. In press.
70. Santulli G, et al. CaMK4 gene deletion induces hypertension. J Am Heart Assoc. 2012;1(4):e001081.
71. Dukes ID, et al. Defective pancreatic β-cell glycolytic signaling in hepatocyte nuclear factor-1α-deficient mice. J Biol Chem. 1998;273(38):24457-24464.
72. Fusco A, et al. Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis. Cell Sig. 2012;24(2):468-475.
73. +/- mice. J Clin Invest. 2003;111(8):1147-1160.
74. Cheung JW, et al. Short-coupled polymorphic ventricular tachycardia at rest linked to a novel ryanodine receptor (RyR2) mutation: leaky RyR2 channels under non-stress conditions. Int J Cardiol. 2015;180:228-236.
75. Sorriento D, Santulli G, Fusco A, Anastasio A, Trimarco B, Iaccarino G. Intracardiac injection of AdGRK5-NT reduces left ventricular hypertrophy by inhibiting NF-κB-dependent hypertrophic gene expression. Hypertension. 2010;56(4):696-704.
76. Santulli G, et al. A selective microRNA-based strategy inhibits restenosis while preserving endothelial function. J Clin Invest. 2014;124(9):4102-4114.